Millions of people worldwide suffer from bone diseases, predisposing them to fractures and related comorbidities that have devastating consequences. Imaging plays an important role in fracture risk assessment, diagnosis, staging, and treatment monitoring of patients with bone diseases. Flexibility of MRI has paved the way for non-invasive assessment of bone quality at multiple levels, including trabecular and cortical bone. This talk will provide an overview of emerging MR-based approaches for quantifying bone quality in human subjects, including pulse sequences, data acquisition, image processing, and validation studies.
Clinical Problem
Millions of people worldwide suffer from bone diseases, predisposing them to fractures and related comorbidities that have devastating consequences. Within a year of a hip fracture, 20-30% of patients will die and 50% will lose the ability to walk [1-3].Role of Imaging
Imaging plays an important role in fracture risk assessment, diagnosis, staging, and treatment monitoring of patients with bone diseases. Radiographs and dual energy X-ray absorptiometry (DXA), which provide semi-quantitative assessment, are the modalities of choice for clinical management of metabolic bone diseases. Recent advances in ultrasonography, nuclear medicine, computed tomography, and magnetic resonance imaging (MRI) have enabled numerous non-invasive techniques for quantification of bone quality. In particular, the flexibility of MRI has paved the way for non-invasive assessment of bone quality at multiple levels, including trabecular and cortical bone.Assessment of Trabecular Bone
Three dimensional microstructure of trabecular bone in human subjects can be visualized using high-resolution MRI [4, 5]. Early MRI studies of trabecular bone were limited to skeletal extremities such as the distal radius, calcaneus, distal tibia, proximal tibia, and distal femur. More recently, it has been shown that the proximal femur - - the site of most traumatic fracture - - can be imaged at resolutions sufficient to resolve individual trabeculae using spin-echo [6] and gradient-echo [7] techniques. High-resolution imaging of trabecular bone has paved the way for elegant image analysis algorithms for extracting information about various aspects of bone quality not previously feasible. For example, it is now possible to characterize trabecular bone microarchitecture using techniques such as digital topological analysis [8] and geodesic topological analysis [9].Assessment of Cortical Bone
80% of the weight of an adult human skeleton is cortical bone [10] and in the femoral neck, load is shared almost equally between trabecular and cortical bone compartments [11]. Deterioration of intrinsic material properties, as well as structural changes such as increased intracortical porosity, thinning of the cortex, trabecularization of the endocortical regions, and periosteal expansion contribute to reduced mechanical competence of cortical bone [12, 13]. Direct imaging has been applied to assess cortical bone porosity [14], however, this type of technology can resolve only the largest pores due to limitations in spatial resolution.Assessment of Bone Strength
High-resolution bone imaging data can be used to generate subject-specific computer models. These models allow simulation of typical loading conditions on bone such as during stance or fall to the side. Through such simulations it is possible to determine bone strength and predict fracture susceptibility in a subject-specific manner [15-17].Assessment of Bone Water
Newer efforts have focused on understanding factors other than bone mineral density that affect cortical bone porosity, and as such it has recently been proposed that bone water be utilized as a MRI biomarker of cortical bone quality [18]. Cortical bone has T2 relaxation times on the order of only a few hundred microseconds and cannot be detected with conventional imaging techniques where echo times are on the order of milliseconds. Ultrashort echo time (UTE) MRI allows for echo times less than 100 microseconds, paving the way for direct signal detection from short-T2 species such as cortical bone. Several novel methods based on UTE MRI have been proposed and validated for the assessment of cortical porosity in human subjects [19-21], and new attempts have been made to achieve differential detection of signal arising from various water pools within cortical bone, resulting from recognition that water bound to collagen and water residing in pore spaces correlate positively and negatively, respectively, with mechanical competence [22]. Horch et al developed a UTE-based sequence to obtain signal from predominantly bound or pore water by incorporating T2 selective single or double adiabatic inversion pulses, respectively [23]. Biswas et al proposed another UTE-based method to separate bound and pore water signals via biexponential analysis of signal decay by exploiting the differences in T2* relaxation times between the two water components [24].1. Brauer, C.A., et al., Incidence and mortality of hip fractures in the United States. Jama, 2009. 302(14): p. 1573-9.
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